‘Silver bullet’ solutions in NZ antibiotic research
28 August 2017
Amidst the burgeoning threats of a global “antibiotic apocalypse” and a major New Zealand health crisis hospitalising more than 100 children every year, two leading researchers from Victoria University of Wellington are breaking new ground in the fight against pathogens and will introduce their work at an upcoming Spotlight Lecture focusing on antibiotics, drug discovery and penicillin prevention of rheumatic fever.
Developing novel antibiotics, including re-imagining the age-old use of silver to treat infection, is the focus of work by Dr Darren Day in Victoria’s Centre for Biodiscovery, while Dr Dianne Sika-Paotonu from the Faculty of Health is focused on a new formulation and delivery method of penicillin used for rheumatic fever.
Silver has been used for centuries to kill germs and bacteria, and even ward off or destroy evil, so its beneficial properties are widely accepted. But what Day and his team are working on is a ‘silver bullet’ in the form of an innovative method of using aptamers (synthetic antibodies) to deliver medicines to specific targets – in this case Pseudomonas aeruginosa, an “opportunistic bacterium” commonly infecting those with compromised immune systems that is ranked by the World Health Organisation in 2017 as the second greatest microbial threat to human health and in dire need of new antibiotics to treat it.
“Aptamers are essentially chemical antibodies which are selected to target specific pathogens. We have joined these aptamers targeted at P. aeruginosa to medicinal silver – which has been known since 4000 BC to be incredibly effective in treating infections,” says Day.
“In larger doses silver can be toxic, but what we have done with the aptamers is ensure specific delivery to the bacteria and not to the surrounding cells. These ‘aptabiotics’ are quick to produce compared to antibodies, drug molecules, including nanomaterials, can easily be incorporated into their structure to target specific cells, and they kill bacteria incredibly rapidly.”
Initial testing by Day and his team has proven highly successful, and the team is expanding trials with the cutting-edge process they have now patented.
“We’re the only ones doing this at the moment, and it’s a little bit out there. People never thought about delivering silver directly to the cells themselves. What we’re trying to do now is tailor these aptamers to other pathogens,” Day says.
Although the need for a new range of antibiotics to combat the ever-growing number of resistant bugs is essential, for diseases like rheumatic fever, penicillin is still the best response and preventative measure we have.
Considered an illness of developing countries, acute rheumatic fever (ARF) is an autoimmune condition caused by untreated group A streptococcal (GAS) bacterial infections of the throat (and possibly skin) which causes the heart, joints, brain and skin to become inflamed and swollen. Multiple or severe attacks of ARF can cause permanent heart damage known as rheumatic heart disease (RHD).
Painful monthly injections of the antibiotic Benzathine Penicillin G (BPG) are given for at least 10 years to prevent further GAS infections that can lead to ARF and cause RHD. New Zealand has high rates of ARF, with Māori and Pacific children and young people aged 5-14 years most affected.
Together with collaborators, Sika-Paotonu’s work is concerned with the ongoing prevention of ARF by reformulating the monthly penicillin injections required to prevent further GAS infections that could cause another bout of the condition.
“These monthly injections are needed for at least a decade and sometimes a lifetime, and by all accounts each injection is very painful. A new penicillin for ARF/RHD is urgently needed,” says Sika-Paotonu.
“A vaccine against GAS is on its way, but will take time, so we are looking at how to better manage this disease in the interim. Penicillin works great, but the injections are horrible. We are part of a global effort to reformulate BPG to make it less painful to give and hopefully last longer.”
Another important component of Sika-Paotonu’s research is finding out how BPG actually works in the bodies of those most affected.
“The initial studies were carried out in the 1950s to determine how BPG would work, but they gave injections to soldiers in the US who were all fit, healthy European men aged 18-24. The data was then used to determine how we use penicillin today on very different groups of people, including sick young people. Clearly there’s a huge gap in the research around this which we are also looking to fill,” Sika-Paotonu says.
“This is a major health issue in New Zealand, and globally, that we need to continue raising awareness about while we work to address it.”